The primary function of male reproduction is to produce sperm for the propagation of the species. Regulation of this process is under the control of various hormonal agents released by the testes and the pituitary. Minor alterations in the concentrations of these humoral agents in the body lead to he disruption of spermatogenesis in both man and other mammals. In some instances, toxic environmental agents can also induce a disruption of spermatogenesis. The United States Environmental Protection Agency has commissioned three studies, two on known male reproductive toxins and one on a suspected male reproductive toxin, to establish the efficacy of a technique for estimating the potency of toxic agents on male reproduction. The technique consists of measuring the weights of the male reproductive organs, testicular sperm content, epididymal sperm content, sperm motility and morphology, following exposure of rats to different concentrations of a toxic substance for at least 6 cycles of the germinal epithelium. Determination of these parameters will certainly establish whether a toxin will have an effect on male reproduction, as well as yield an estimate of the toxin's potency. However, additional paramaters need to be monitored to gain insights into the mechanisms of action of these toxins so that appropriate measures may be taken to treat exposed individuals. This proposal requests support for investigation of the mechanisms of action of 3 toxins on male reproduction through analysis of tissue samples generated in previous studies. The specific analyses to be done are: 1) serum levels of follicle stimulating hormone and luteinizing hormone; 2) serum levels of testosterone; 3) testicular capacity for testosterone secretion; 4) morphometric analysis of the testicular germinal epithelium. Determination of these parameters will establish whether the pituitary-testicular hormonal axis has been disrupted by the toxins, as well as the developmental stage of spermatogenesis that has been affected.